A study led by researchers at the Perelman School of Medicine at the University of Pennsylvania has found that a new blood test panel may improve detection rates for pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer. The findings were published in Clinical Cancer Research, a journal from the American Association for Cancer Research.
The research team evaluated a biomarker panel that includes four proteins: ANPEP, PIGR, CA19-9, and THBS2. Their analysis showed that this combination was more effective in identifying PDAC than using CA19-9 alone, which is currently widely used to monitor diagnosed pancreatic cancer but not recommended as a standalone screening tool due to its limitations.
Kenneth S. Zaret, PhD, senior author and professor of Cell and Developmental Biology, explained the motivation behind the study: “Pancreatic cancer usually doesn't present with symptoms until it's too late for surgery, when the cancer has already metastasized to other parts of the body. Our goal was to look for biomarkers in the blood that appear in early-stage PDAC patients, to catch the disease early.”
CA19-9 is released into the blood by both normal and cancerous pancreatic cells; however, its effectiveness as an early screening tool is limited because benign conditions can also elevate its levels or some patients with PDAC may have low CA19-9 despite having cancer. THBS2 has shown potential as an investigational marker but has had mixed results when used alone.
To identify new biomarkers, researchers analyzed plasma samples from two groups: 537 samples from Mayo Clinic and 135 from Hospital of the University of Pennsylvania. These included patients with confirmed pancreatic cancer, healthy individuals, and those with benign pancreatic diseases. This allowed them to compare protein levels across different conditions.
They found that ANPEP (aminopeptidase N) and PIGR (polymeric immunoglobulin receptor) were elevated in early-stage PDAC cases compared to non-cancer controls. By combining these two markers with CA19-9 and THBS2 into one panel, they achieved high accuracy rates—area under curve (AUC) values of 0.97 and 0.96—when distinguishing between stage 1–2 PDAC patients and healthy individuals across both cohorts.
The four-marker panel identified 91.9 percent of all stages of pancreatic cancers and 87.5 percent of early-stage cases overall; by comparison, CA19-9 alone detected 82.7 percent overall and 76.2 percent at early stages—a statistically significant improvement for all-stage detection.
Zaret noted that if these results are confirmed through larger prospective studies involving people at increased risk for pancreatic cancer—including those with family history or genetic mutations—the test could help clinicians decide who would benefit from follow-up imaging earlier on: “With the addition of ANPEP and PIGR, the panel helps to overcome known limitations associated with CA19-9 and THBS2 testing—such as patients who genetically underexpress CA19-9 or tumors that present as different molecular subtypes—and could therefore reduce the number of missed cancer cases while keeping false positives low,” he said.
He also pointed out limitations such as not including high-risk individuals like those with BRCA mutations or new-onset diabetes in their cohorts; additionally, since this was a retrospective study design rather than prospective real-world screening trial, further research will be needed before clinical adoption.
Funding support came from several organizations including National Institutes of Health, Penn Pancreatic Cancer Research Center, A Love for Life foundation, Lustgarten Foundation, Centene Foundation and Mayo Clinic Comprehensive Cancer Center. Zaret declared no conflicts of interest.
